Threshold of dopamine D_2/3 receptor occupancy for hyperprolactinemia in older patients with schizophrenia

Objective: Although hyperprolactinemia carries a long-Term risk of morbidity, the threshold of dopamine D2/3 receptor (D2/3R) occupancy for hyperprolactinemia has not been investigated in older patients with schizophrenia. Data were taken from a positron emission tomography (PET) study conducted between August 2007 and August 2015. The present post hoc study included 42 clinically stable outpatients with schizophrenia (DSM-IV) (mean SD age = 60.2 6.7 years) taking olanzapine or risperidone. Subjects underwent [11C]-raclopride PET scans to measure D2/3R occupancy before and after reducing their dose of antipsychotic by up to 40%. Blood samples were collected before each PET scan to measure prolactin levels. Methods: The relationship between prolactin levels and D_2/3R occupancy was examined using stepwise linear regression analyses. The D2/3R occupancy thresholds for hyperprolactinemia were explored using Fisher exact tests. Results: Prolactin levels decreased following dose reduction (mean SD = 24.1 30.2 ng/mL to 17.2 15.1 ng/mL; P < .001). Prolactin levels were associated with female gender (β = .32, P = .006, vs male), antipsychotics (β = .23, P = .02, risperidone vs olanzapine), and D_2/3R occupancy (β = .23, P = .04). Those with D_2/3R occupancy of 66% or higher were more likely to have hyperprolactinemia than those with D_2/3R occupancy lower than 66% (P = .03). Sensitivity, specificity, positive predictive value, and negative predictive value of this threshold were 0.44, 0.81, 0.78, and 0.48, respectively. We identified a D_2/3R occupancy threshold for hyperprolactinemia of 66% in older patients with schizophrenia, which is lower than that reported in younger patients (73%) by other researchers. Conclusions: Our results suggest a higher sensitivity to antipsychotics in older patients. Prolactin levels could assist in the determination of appropriate antipsychotic dosing to minimize adverse effects.